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Author Asvold, B.O.; Bjorngaard, J.H.; Carslake, D.; Gabrielsen, M.E.; Skorpen, F.; Davey Smith, G.; Romundstad, P.R. url  doi
  Title Causal associations of tobacco smoking with cardiovascular risk factors: a Mendelian randomization analysis of the HUNT Study in Norway Type Journal Article
  Year 2014 Publication International Journal of Epidemiology Abbreviated Journal Int J Epidemiol  
  Volume 43 Issue 5 Pages 1458-1470  
  Keywords HUNT3; Smoking; blood pressure; body mass index; cholesterol; glomerular filtration rate; heart rate  
  Abstract BACKGROUND: Tobacco smoking has been associated with cardiovascular risk factors including adverse serum lipid levels, central obesity and higher resting heart rate, but lower blood pressure and body mass index (BMI). We used a Mendelian randomization approach to study whether these associations may be causal. If smoking affects cardiovascular risk factors then rs1051730 T alleles, predictors of increased smoking quantity, should be associated with cardiovascular risk factors among smokers, but not among never smokers. METHODS: Among 56 625 participants of a population-based study, we estimated associations of rs1051730 T alleles with cardiovascular risk factors and examined whether the associations differed by smoking status. RESULTS: Rs1051730 T alleles were associated with lower BMI and waist and hip circumferences and higher resting heart rate and estimated glomerular filtration rate (eGFR), and the associations were strongest among current smokers (P interaction 5 x 10(-9) to 0.01). Rs1051730 T alleles were associated with lower systolic blood pressure and pulse pressure and higher HDL cholesterol concentrations, but these associations did not robustly differ by smoking status. There were no convincing associations of rs1051730 T alleles with waist-hip ratio, diastolic blood pressure and non-fasting serum concentrations of non-HDL cholesterol, triglycerides, glucose and C-reactive protein. CONCLUSIONS: This Mendelian randomization analysis provides evidence that smoking may cause lower BMI and waist and hip circumferences and higher resting heart rate and eGFR. The findings further suggest that smoking is not a major determinant of waist-hip ratio or adverse blood pressure, serum lipid or glucose levels.  
  Address Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway, Department of Endocrinology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway, MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, UK, Department of Cancer Research and Molecular Medicine and Department of Laboratory Medicine, Children's and Women's Health, Norwegian University of Science and Technology, Trondheim, Norway  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0300-5771 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:24867305 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1636  
Permanent link to this record
 

 
Author Dastani, Z.; Hivert, M.-F.; Timpson, N.; Perry, J.R.B.; Yuan, X.; Scott, R.A.; Henneman, P.; Heid, I.M.; Kizer, J.R.; Lyytikainen, L.-P.; Fuchsberger, C.; Tanaka, T.; Morris, A.P.; Small, K.; Isaacs, A.; Beekman, M.; Coassin, S.; Lohman, K.; Qi, L.; Kanoni, S.; Pankow, J.S.; Uh, H.-W.; Wu, Y.; Bidulescu, A.; Rasmussen-Torvik, L.J.; Greenwood, C.M.T.; Ladouceur, M.; Grimsby, J.; Manning, A.K.; Liu, C.-T.; Kooner, J.; Mooser, V.E.; Vollenweider, P.; Kapur, K.A.; Chambers, J.; Wareham, N.J.; Langenberg, C.; Frants, R.; Willems-Vandijk, K.; Oostra, B.A.; Willems, S.M.; Lamina, C.; Winkler, T.W.; Psaty, B.M.; Tracy, R.P.; Brody, J.; Chen, I.; Viikari, J.; Kahonen, M.; Pramstaller, P.P.; Evans, D.M.; St Pourcain, B.; Sattar, N.; Wood, A.R.; Bandinelli, S.; Carlson, O.D.; Egan, J.M.; Bohringer, S.; van Heemst, D.; Kedenko, L.; Kristiansson, K.; Nuotio, M.-L.; Loo, B.-M.; Harris, T.; Garcia, M.; Kanaya, A.; Haun, M.; Klopp, N.; Wichmann, H.-E.; Deloukas, P.; Katsareli, E.; Couper, D.J.; Duncan, B.B.; Kloppenburg, M.; Adair, L.S.; Borja, J.B.; Wilson, J.G.; Musani, S.; Guo, X.; Johnson, T.; Semple, R.; Teslovich, T.M.; Allison, M.A.; Redline, S.; Buxbaum, S.G.; Mohlke, K.L.; Meulenbelt, I.; Ballantyne, C.M.; Dedoussis, G.V.; Hu, F.B.; Liu, Y.; Paulweber, B.; Spector, T.D.; Slagboom, P.E.; Ferrucci, L.; Jula, A.; Perola, M.; Raitakari, O.; Florez, J.C.; Salomaa, V.; Eriksson, J.G.; Frayling, T.M.; Hicks, A.A.; Lehtimaki, T.; Smith, G.D.; Siscovick, D.S.; Kronenberg, F.; van Duijn, C.; Loos, R.J.F.; Waterworth, D.M.; Meigs, J.B.; Dupuis, J.; Richards, J.B.; Voight, B.F.; Scott, L.J.; Steinthorsdottir, V.; Dina, C.; Welch, R.P.; Zeggini, E.; Huth, C.; Aulchenko, Y.S.; Thorleifsson, G.; McCulloch, L.J.; Ferreira, T.; Grallert, H.; Amin, N.; Wu, G.; Willer, C.J.; Raychaudhuri, S.; McCarroll, S.A.; Hofmann, O.M.; Segre, A.V.; van Hoek, M.; Navarro, P.; Ardlie, K.; Balkau, B.; Benediktsson, R.; Bennett, A.J.; Blagieva, R.; Boerwinkle, E.; Bonnycastle, L.L.; Bostrom, K.B.; Bravenboer, B.; Bumpstead, S.; Burtt, N.P.; Charpentier, G.; Chines, P.S.; Cornelis, M.; Crawford, G.; Doney, A.S.F.; Elliott, K.S.; Elliott, A.L.; Erdos, M.R.; Fox, C.S.; Franklin, C.S.; Ganser, M.; Gieger, C.; Grarup, N.; Green, T.; Griffin, S.; Groves, C.J.; Guiducci, C.; Hadjadj, S.; Hassanali, N.; Herder, C.; Isomaa, B.; Jackson, A.U.; Johnson, P.R.V.; Jorgensen, T.; Kao, W.H.L.; Kong, A.; Kraft, P.; Kuusisto, J.; Lauritzen, T.; Li, M.; Lieverse, A.; Lindgren, C.M.; Lyssenko, V.; Marre, M.; Meitinger, T.; Midthjell, K.; Morken, M.A.; Narisu, N.; Nilsson, P.; Owen, K.R.; Payne, F.; Petersen, A.-K.; Platou, C.; Proenca, C.; Prokopenko, I.; Rathmann, W.; Rayner, N.W.; Robertson, N.R.; Rocheleau, G.; Roden, M.; Sampson, M.J.; Saxena, R.; Shields, B.M.; Shrader, P.; Sigurdsson, G.; Sparso, T.; Strassburger, K.; Stringham, H.M.; Sun, Q.; Swift, A.J.; Thorand, B.; Tichet, J.; Tuomi, T.; van Dam, R.M.; van Haeften, T.W.; van Herpt, T.; van Vliet-Ostaptchouk, J.V.; Walters, G.B.; Weedon, M.N.; Wijmenga, C.; Witteman, J.; Bergman, R.N.; Cauchi, S.; Collins, F.S.; Gloyn, A.L.; Gyllensten, U.; Hansen, T.; Hide, W.A.; Hitman, G.A.; Hofman, A.; Hunter, D.J.; Hveem, K.; Laakso, M.; Morris, A.D.; Palmer, C.N.A.; Rudan, I.; Sijbrands, E.; Stein, L.D.; Tuomilehto, J.; Uitterlinden, A.; Walker, M.; Watanabe, R.M.; Abecasis, G.R.; Boehm, B.O.; Campbell, H.; Daly, M.J.; Hattersley, A.T.; Pedersen, O.; Barroso, I.; Groop, L.; Sladek, R.; Thorsteinsdottir, U.; Wilson, J.F.; Illig, T.; Froguel, P.; van Duijn, C.M.; Stefansson, K.; Altshuler, D.; Boehnke, M.; McCarthy, M.I.; Soranzo, N.; Wheeler, E.; Glazer, N.L.; Bouatia-Naji, N.; Magi, R.; Randall, J.; Elliott, P.; Rybin, D.; Dehghan, A.; Hottenga, J.J.; Song, K.; Goel, A.; Lajunen, T.; Doney, A.; Cavalcanti-Proenca, C.; Kumari, M.; Timpson, N.J.; Zabena, C.; Ingelsson, E.; An, P.; O'Connell, J.; Luan, J.'an; Elliott, A.; McCarroll, S.A.; Roccasecca, R.M.; Pattou, F.; Sethupathy, P.; Ariyurek, Y.; Barter, P.; Beilby, J.P.; Ben-Shlomo, Y.; Bergmann, S.; Bochud, M.; Bonnefond, A.; Borch-Johnsen, K.; Bottcher, Y.; Brunner, E.; Bumpstead, S.J.; Chen, Y.-D.I.; Chines, P.; Clarke, R.; Coin, L.J.M.; Cooper, M.N.; Crisponi, L.; Day, I.N.M.; de Geus, E.J.C.; Delplanque, J.; Fedson, A.C.; Fischer-Rosinsky, A.; Forouhi, N.G.; Franzosi, M.G.; Galan, P.; Goodarzi, M.O.; Graessler, J.; Grundy, S.; Gwilliam, R.; Hallmans, G.; Hammond, N.; Han, X.; Hartikainen, A.-L.; Hayward, C.; Heath, S.C.; Hercberg, S.; Hillman, D.R.; Hingorani, A.D.; Hui, J.; Hung, J.; Kaakinen, M.; Kaprio, J.; Kesaniemi, Y.A.; Kivimaki, M.; Knight, B.; Koskinen, S.; Kovacs, P.; Kyvik, K.O.; Lathrop, G.M.; Lawlor, D.A.; Le Bacquer, O.; Lecoeur, C.; Li, Y.; Mahley, R.; Mangino, M.; Martinez-Larrad, M.T.; McAteer, J.B.; McPherson, R.; Meisinger, C.; Melzer, D.; Meyre, D.; Mitchell, B.D.; Mukherjee, S.; Naitza, S.; Neville, M.J.; Orru, M.; Pakyz, R.; Paolisso, G.; Pattaro, C.; Pearson, D.; Peden, J.F.; Pedersen, N.L.; Pfeiffer, A.F.H.; Pichler, I.; Polasek, O.; Posthuma, D.; Potter, S.C.; Pouta, A.; Province, M.A.; Rayner, N.W.; Rice, K.; Ripatti, S.; Rivadeneira, F.; Rolandsson, O.; Sandbaek, A.; Sandhu, M.; Sanna, S.; Sayer, A.A.; Scheet, P.; Seedorf, U.; Sharp, S.J.; Shields, B.; Sigurethsson, G.; Sijbrands, E.J.G.; Silveira, A.; Simpson, L.; Singleton, A.; Smith, N.L.; Sovio, U.; Swift, A.; Syddall, H.; Syvanen, A.-C.; Tonjes, A.; Uitterlinden, A.G.; van Dijk, K.W.; Varma, D.; Visvikis-Siest, S.; Vitart, V.; Vogelzangs, N.; Waeber, G.; Wagner, P.J.; Walley, A.; Ward, K.L.; Watkins, H.; Wild, S.H.; Willemsen, G.; Witteman, J.C.M.; Yarnell, J.W.G.; Zelenika, D.; Zethelius, B.; Zhai, G.; Zhao, J.H.; Zillikens, M.C.; Borecki, I.B.; Meneton, P.; Magnusson, P.K.E.; Nathan, D.M.; Williams, G.H.; Silander, K.; Bornstein, S.R.; Schwarz, P.; Spranger, J.; Karpe, F.; Shuldiner, A.R.; Cooper, C.; Serrano-Rios, M.; Lind, L.; Palmer, L.J.; Hu, F.B. 1st; Franks, P.W.; Ebrahim, S.; Marmot, M.; Kao, W.H.L.; Pramstaller, P.P.; Wright, A.F.; Stumvoll, M.; Hamsten, A.; Buchanan, T.A.; Valle, T.T.; Rotter, J.I.; Penninx, B.W.J.H.; Boomsma, D.I.; Cao, A.; Scuteri, A.; Schlessinger, D.; Uda, M.; Ruokonen, A.; Jarvelin, M.-R.; Peltonen, L.; Mooser, V.; Sladek, R.; Musunuru, K.; Smith, A.V.; Edmondson, A.C.; Stylianou, I.M.; Koseki, M.; Pirruccello, J.P.; Chasman, D.I.; Johansen, C.T.; Fouchier, S.W.; Peloso, G.M.; Barbalic, M.; Ricketts, S.L.; Bis, J.C.; Feitosa, M.F.; Orho-Melander, M.; Melander, O.; Li, X.; Li, M.; Cho, Y.S.; Go, M.J.; Kim, Y.J.; Lee, J.-Y.; Park, T.; Kim, K.; Sim, X.; Ong, R.T.-H.; Croteau-Chonka, D.C.; Lange, L.A.; Smith, J.D.; Ziegler, A.; Zhang, W.; Zee, R.Y.L.; Whitfield, J.B.; Thompson, J.R.; Surakka, I.; Spector, T.D.; Smit, J.H.; Sinisalo, J.; Scott, J.; Saharinen, J.; Sabatti, C.; Rose, L.M.; Roberts, R.; Rieder, M.; Parker, A.N.; Pare, G.; O'Donnell, C.J.; Nieminen, M.S.; Nickerson, D.A.; Montgomery, G.W.; McArdle, W.; Masson, D.; Martin, N.G.; Marroni, F.; Lucas, G.; Luben, R.; Lokki, M.-L.; Lettre, G.; Launer, L.J.; Lakatta, E.G.; Laaksonen, R.; Kyvik, K.O.; Konig, I.R.; Khaw, K.-T.; Kaplan, L.M.; Johansson, A.; Janssens, A.C.J.W.; Igl, W.; Hovingh, G.K.; Hengstenberg, C.; Havulinna, A.S.; Hastie, N.D.; Harris, T.B.; Haritunians, T.; Hall, A.S.; Groop, L.C.; Gonzalez, E.; Freimer, N.B.; Erdmann, J.; Ejebe, K.G.; Doring, A.; Dominiczak, A.F.; Demissie, S.; Deloukas, P.; de Faire, U.; Crawford, G.; Chen, Y.-der I.; Caulfield, M.J.; Boekholdt, S.M.; Assimes, T.L.; Quertermous, T.; Seielstad, M.; Wong, T.Y.; Tai, E.-S.; Feranil, A.B.; Kuzawa, C.W.; Taylor, H.A.J.; Gabriel, S.B.; Holm, H.; Gudnason, V.; Krauss, R.M.; Ordovas, J.M.; Munroe, P.B.; Kooner, J.S.; Tall, A.R.; Hegele, R.A.; Kastelein, J.J.P.; Schadt, E.E.; Strachan, D.P.; Reilly, M.P.; Samani, N.J.; Schunkert, H.; Cupples, L.A.; Sandhu, M.S.; Ridker, P.M.; Rader, D.J.; Kathiresan, S. url  doi
  Title Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals Type Journal Article
  Year 2012 Publication PLoS Genetics Abbreviated Journal PLoS Genet  
  Volume 8 Issue 3 Pages e1002607  
  Keywords Adiponectin/*blood/genetics; African Americans; Asian Continental Ancestry Group; Cholesterol, HDL/genetics; Diabetes Mellitus, Type 2/*genetics; European Continental Ancestry Group; Female; Gene Expression; Genetic Predisposition to Disease; *Genome-Wide Association Study; Glucose Tolerance Test; Humans; Insulin Resistance/genetics; Male; Metabolic Networks and Pathways; Polymorphism, Single Nucleotide; Waist-Hip Ratio  
  Abstract Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5x10(-8)-1.2x10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3x10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3x10(-3), n = 22,044), increased triglycerides (p = 2.6x10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8x10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4x10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5x10(-13), n = 96,748) and decreased BMI (p = 1.4x10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.  
  Address Department of Epidemiology, Biostatistics, and Occupational Health, Jewish General Hospital, Lady Davis Institute, McGill University, Montreal, Canada  
  Corporate Author GLGC Consortium Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1553-7390 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:22479202; PMC3315470 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1516  
Permanent link to this record
 

 
Author Ernstsen, L.; Strand, B.H.; Nilsen, S.M.; Espnes, G.A.; Krokstad, S. url  doi
  Title Trends in absolute and relative educational inequalities in four modifiable ischaemic heart disease risk factors: repeated cross-sectional surveys from the Nord-Trondelag Health Study (HUNT) 1984-2008 Type Journal Article
  Year 2012 Publication BMC Public Health Abbreviated Journal BMC Public Health  
  Volume 12 Issue Pages 266  
  Keywords Adult; Cross-Sectional Studies; Diabetes Mellitus/*epidemiology; *Educational Status; Female; Humans; Hypercholesterolemia/*epidemiology; Hypertension/*epidemiology; Male; Middle Aged; Myocardial Ischemia/*epidemiology; Norway/epidemiology; Risk Factors; Smoking/*epidemiology  
  Abstract BACKGROUND: There has been an overall decrease in incident ischaemic heart disease (IHD), but the reduction in IHD risk factors has been greater among those with higher social position. Increased social inequalities in IHD mortality in Scandinavian countries is often referred to as the Scandinavian “public health puzzle”. The objective of this study was to examine trends in absolute and relative educational inequalities in four modifiable ischaemic heart disease risk factors (smoking, diabetes, hypertension and high total cholesterol) over the last three decades among Norwegian middle-aged women and men. METHODS: Population-based, cross-sectional data from The Nord-Trondelag Health Study (HUNT): HUNT 1 (1984-1986), HUNT 2 (1995-1997) and HUNT 3 (2006-2008), women and men 40-59 years old. Educational inequalities were assessed using the Slope Index of Inequality (SII) and The Relative Index of Inequality (RII). RESULTS: Smoking prevalence increased for all education groups among women and decreased in men. Relative and absolute educational inequalities in smoking widened in both genders, with significantly higher absolute inequalities among women than men in the two last surveys. Diabetes prevalence increased in all groups. Relative inequalities in diabetes were stable, while absolute inequalities increased both among women (p = 0.05) and among men (p = 0.01). Hypertension prevalence decreased in all groups. Relative inequalities in hypertension widened over time in both genders. However, absolute inequalities in hypertension decreased among women (p = 0.05) and were stable among men (p = 0.33). For high total cholesterol relative and absolute inequalities remained stable in both genders. CONCLUSION: Widening absolute educational inequalities in smoking and diabetes over the last three decades gives rise to concern. The mechanisms behind these results are less clear, and future studies are needed to assess if educational inequalities in secondary prevention of IHD are larger compared to educational inequalities in primary prevention of IHD. Continued monitoring of IHD risk factors at the population level is therefore warranted. The results emphasise the need for public health efforts to prevent future burdens of life-style-related diseases and to avoid further widening in socioeconomic inequalities in IHD mortality in Norway, especially among women.  
  Address Sor-Trondelag University College, Mauritz Hansens gt 2, 7004, Trondheim, Norway. linda.ernstsen@hist.no  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1471-2458 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:22471945; PMC3434116 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1524  
Permanent link to this record
 

 
Author Gudmundsdottir, S.L.; Flanders, W.D.; Augestad, L.B. url  doi
  Title Physical activity and cardiovascular risk factors at menopause: the Nord-Trondelag health study Type Journal Article
  Year 2013 Publication Climacteric : the Journal of the International Menopause Society Abbreviated Journal Climacteric  
  Volume 16 Issue 4 Pages 438-446  
  Keywords Adult; Blood Glucose/analysis; Blood Pressure; Body Mass Index; Body Weight; Cardiovascular Diseases/*epidemiology; Cholesterol, HDL/blood; *Exercise; Female; Follow-Up Studies; Health Surveys; Humans; *Menopause; Metabolic Diseases/epidemiology; Middle Aged; Norway/epidemiology; Premenopause/physiology; Questionnaires; Risk Factors; Triglycerides/blood; Waist-Hip Ratio  
  Abstract BACKGROUND: Lowered physical activity levels may partially explain changes in metabolic risk factors in women after menopause. OBJECTIVES: To evaluate the association between physical activity and metabolic risk factors at baseline and after 11 years, as well as the change in that association over time in women who were premenopausal and >/= 40 years at baseline. METHODS: Subjects in a Norwegian population-based health survey answered questionnaires and had body and serum measurements during 1995-1997 (HUNT 2) and in a follow-up study during 2006-2008 (HUNT 3). Repeated-measures analyses were used to estimate the association between physical activity and metabolic factors, adjusting for age, smoking status, education, alcohol intake, and parity. Adjustment for hormonal treatment and medication was made, as appropriate. RESULTS: In women remaining premenopausal, a higher physical activity score in HUNT 3 was associated with lower weight (p < 0.01) and waist-hip ratio (p < 0.01) and higher high density lipoprotein (HDL) cholesterol in HUNT 3 (p < 0.01). In women that were postmenopausal by the time of follow-up, a higher physical activity score in HUNT 3 was associated with lower weight (p < 0.01), waist-hip ratio (p < 0.01), triglycerides (p < 0.01), and higher total cholesterol (p < 0.05), HDL cholesterol (p < 0.01), and diastolic blood pressure (p < 0.05) in HUNT 3. The association of total physical activity score with weight and waist-hip ratio was stronger in HUNT 3 than in HUNT 2 (p < 0.01). CONCLUSION: Increased physical activity may reduce the risk of adverse outcomes and use of pharmacological management in women of menopausal age.  
  Address Department of Human Movement Science, Norwegian University of Science and Technology, Trondheim, Norway  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1369-7137 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23347190 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1450  
Permanent link to this record
 

 
Author Holmen, O.L.; Zhang, H.; Fan, Y.; Hovelson, D.H.; Schmidt, E.M.; Zhou, W.; Guo, Y.; Zhang, J.; Langhammer, A.; Lochen, M.-L.; Ganesh, S.K.; Vatten, L.; Skorpen, F.; Dalen, H.; Zhang, J.; Pennathur, S.; Chen, J.; Platou, C.; Mathiesen, E.B.; Wilsgaard, T.; Njolstad, I.; Boehnke, M.; Chen, Y.E.; Abecasis, G.R.; Hveem, K.; Willer, C.J. url  doi
  Title Systematic evaluation of coding variation identifies a candidate causal variant in TM6SF2 influencing total cholesterol and myocardial infarction risk Type Journal Article
  Year 2014 Publication Nature Genetics Abbreviated Journal Nat Genet  
  Volume 46 Issue 4 Pages 345-351  
  Keywords Animals; Cholesterol, LDL/blood/genetics; Exome/genetics; Gene Knockdown Techniques; *Genetic Variation; Genome-Wide Association Study; Genotype; Humans; Lipids/*blood/genetics; Membrane Proteins/*genetics; Mice; Mice, Inbred C57BL; Mutation, Missense/genetics; Myocardial Infarction/*epidemiology/*genetics; Norway/epidemiology; Risk Factors  
  Abstract Blood lipid levels are heritable, treatable risk factors for cardiovascular disease. We systematically assessed genome-wide coding variation to identify new genes influencing lipid traits, fine map known lipid loci and evaluate whether low-frequency variants with large effects exist for these traits. Using an exome array, we genotyped 80,137 coding variants in 5,643 Norwegians. We followed up 18 variants in 4,666 Norwegians and identified ten loci with coding variants associated with a lipid trait (P < 5 x 10(-8)). One variant in TM6SF2 (encoding p.Glu167Lys), residing in a known genome-wide association study locus for lipid traits, influences total cholesterol levels and is associated with myocardial infarction. Transient TM6SF2 overexpression or knockdown of Tm6sf2 in mice alters serum lipid profiles, consistent with the association observed in humans, identifying TM6SF2 as a functional gene within a locus previously known as NCAN-CILP2-PBX4 or 19p13. This study demonstrates that systematic assessment of coding variation can quickly point to a candidate causal gene.  
  Address 1] Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA. [2] Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA. [3] Department of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1061-4036 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:24633158 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1597  
Permanent link to this record
 

 
Author Kvaloy, K.; Holmen, J.; Hveem, K.; Holmen, T.L. url  doi
  Title Genetic Effects on Longitudinal Changes from Healthy to Adverse Weight and Metabolic Status – The HUNT Study Type Journal Article
  Year 2015 Publication PLoS One Abbreviated Journal PloS one  
  Volume 10 Issue 10 Pages e0139632  
  Keywords HUNT2; HUNT3; Adolescent; Adult; Apolipoproteins A/genetics; Blood Glucose/analysis; Blood Pressure; Body Mass Index; Cholesterol, HDL/blood; Cross-Sectional Studies; Female; Humans; Longitudinal Studies; Male; Metabolic Syndrome X/blood/*etiology/genetics; Middle Aged; Overweight/blood/*complications/*genetics; *Polymorphism, Single Nucleotide; Proteins/genetics; Receptors, Dopamine D2/genetics; Triglycerides/blood; Weight Gain; Young Adult  
  Abstract INTRODUCTION: The complexity of obesity and onset and susceptibility of cardio-metabolic disorders are still poorly understood and is addressed here through studies of genetic influence on weight gain and increased metabolic risk longitudinally. SUBJECTS/METHODS: Twenty seven previously identified obesity, eating disorder or metabolic risk susceptibility SNPs were tested for association with weight or metabolically related traits longitudinally in 3999 adults participating both in the HUNT2 (1995-97) and HUNT3 (2006-08) surveys. Regression analyses were performed with changes from normal weight to overweight/obesity or from metabolically healthy to adverse developments with regards to blood pressure, glucose, HDL cholesterol, triglycerides or metabolic syndrome as outcomes. Additionally, a sub-sample of 1380 adolescents was included for testing association of nine SNPs with longitudinal weight gain into young adulthood. RESULTS: The most substantial effect on BMI-based weight gain from normal to overweight/obesity in adults was observed for the DRD2 variant (rs6277)(OR: 0.79, 95% CI: 0.69-0.90, P = 3.9x10-4, adj. P = 0.015). DRD2 was not associated with BMI on a cross-sectional level. In the adolescent sample, FTO (rs1121980) was associated with change to overweight at adulthood in the combined male-female sample (OR: 1.27, 95% CI: 1.09-1.49, P = 3.0x10-3, adj. P = 0.019) and in females (OR: 1.53, 95% CI: 1.23-1.91, P = 1.8x10-4, adj. P = 0.003). When testing for association to longitudinal adverse developments with regard to blood pressure, blood lipids and glucose, only rs964184 (ZNF259/APOA5) was significantly associated to unfavourable triglyceride changes (OR: 1.66, 95% CI: 1.36-2.03, P = 5.7x10-7, adj. P = 0.001). Pleiotropic effects on metabolic traits, however, were observed for several genetic loci cross-sectionally, ZNF259/APOA5, LPL and GRB14 being the most important. CONCLUSIONS: DRD2 exhibits effects on weight gain from normal weight to overweight/obesity in adults, while, FTO is associated to weight gain from adolescence to young adulthood. Unhealthy longitudinal triglyceride development is strongly affected by ZNF259/APOA. Our main finding, linking the DRD2 variant directly to the longitudinal weight gain observed, has not previously been identified. It suggests a genetic pre-disposition involving the dopaminergic signalling pathways known to play a role in food reward and satiety linked mechanisms.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication HUNT Research Center, Department of Public Health and General Practice, Faculty of Medicine, Norwegi Editor  
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  Notes Kvaloy, KirstiHolmen, JosteinHveem, KristianHolmen, Turid Lingaaseng2015/10/09 06:00PLoS One. 2015 Oct 7;10(10):e0139632. doi: 10.1371/journal.pone.0139632. eCollection 2015. Approved no  
  Call Number HUNT @ maria.stuifbergen @ Kvaloy2015 Serial 1833  
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Author Lange, L.A.; Hu, Y.; Zhang, H.; Xue, C.; Schmidt, E.M.; Tang, Z.-Z.; Bizon, C.; Lange, E.M.; Smith, J.D.; Turner, E.H.; Jun, G.; Kang, H.M.; Peloso, G.; Auer, P.; Li, K.-P.; Flannick, J.; Zhang, J.; Fuchsberger, C.; Gaulton, K.; Lindgren, C.; Locke, A.; Manning, A.; Sim, X.; Rivas, M.A.; Holmen, O.L.; Gottesman, O.; Lu, Y.; Ruderfer, D.; Stahl, E.A.; Duan, Q.; Li, Y.; Durda, P.; Jiao, S.; Isaacs, A.; Hofman, A.; Bis, J.C.; Correa, A.; Griswold, M.E.; Jakobsdottir, J.; Smith, A.V.; Schreiner, P.J.; Feitosa, M.F.; Zhang, Q.; Huffman, J.E.; Crosby, J.; Wassel, C.L.; Do, R.; Franceschini, N.; Martin, L.W.; Robinson, J.G.; Assimes, T.L.; Crosslin, D.R.; Rosenthal, E.A.; Tsai, M.; Rieder, M.J.; Farlow, D.N.; Folsom, A.R.; Lumley, T.; Fox, E.R.; Carlson, C.S.; Peters, U.; Jackson, R.D.; van Duijn, C.M.; Uitterlinden, A.G.; Levy, D.; Rotter, J.I.; Taylor, H.A.; Gudnason, V.J.; Siscovick, D.S.; Fornage, M.; Borecki, I.B.; Hayward, C.; Rudan, I.; Chen, Y.E.; Bottinger, E.P.; Loos, R.J.F.; Saetrom, P.; Hveem, K.; Boehnke, M.; Groop, L.; McCarthy, M.; Meitinger, T.; Ballantyne, C.M.; Gabriel, S.B.; O'Donnell, C.J.; Post, W.S.; North, K.E.; Reiner, A.P.; Boerwinkle, E.; Psaty, B.M.; Altshuler, D.; Kathiresan, S.; Lin, D.-Y.; Jarvik, G.P.; Cupples, L.A.; Kooperberg, C.; Wilson, J.G.; Nickerson, D.A.; Abecasis, G.R.; Rich, S.S.; Tracy, R.P.; Willer, C.J. url  doi
  Title Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol Type Journal Article
  Year 2014 Publication American Journal of Human Genetics Abbreviated Journal Am J Hum Genet  
  Volume 94 Issue 2 Pages 233-245  
  Keywords Adult; Aged; Apolipoproteins E/blood/genetics; Cholesterol, LDL/*genetics; Cohort Studies; Dyslipidemias/blood/genetics; *Exome; Female; Follow-Up Studies; *Gene Frequency; Genetic Code; *Genome-Wide Association Study; Genotype; Humans; Lipase/genetics; Male; Middle Aged; Phenotype; *Polymorphism, Single Nucleotide; Proprotein Convertases/genetics; Receptors, LDL/genetics; Sequence Analysis, DNA; Serine Endopeptidases/genetics; HUNT3  
  Abstract Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.  
  Address Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: cristen@umich.edu  
  Corporate Author NHLBI Grand Opportunity Exome Sequencing Project Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0002-9297 ISBN Medium  
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  Notes PMID:24507775; PMC3928660 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1625  
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Author Markovitz, A.R.; Haug, E.B.; Horn, J.; Fraser, A.; Macdonald-Wallis, C.; Tilling, K.; Rimm, E.B.; Missmer, S.A.; Williams, P.L.; Romundstad, P.R.; Asvold, B.O.; Rich-Edwards, J.W. url  doi
  Title Does pregnancy alter life-course lipid trajectories? Evidence from the HUNT Study in Norway Type Journal Article
  Year 2018 Publication Journal of Lipid Research Abbreviated Journal J Lipid Res  
  Volume 59 Issue 12 Pages 2403-2412  
  Keywords Nord-Trondelag Health Study; cholesterol; epidemiology; high density lipoprotein; mixed model; parity; spline; triglycerides  
  Abstract We examined the association between pregnancy and life-course lipid trajectories. Linked data from the Nord-Trondelag Health Study and the Medical Birth Registry of Norway yielded 19,987 parous and 1,625 nulliparous women. Using mixed-effects spline models, we estimated differences in nonfasting lipid levels from before to after first birth in parous women and between parous and nulliparous women. HDL cholesterol (HDL-C) dropped by -4.2 mg/dl (95% CI: -5.0, -3.3) from before to after first birth in adjusted models, a 7% change, and the total cholesterol (TC) to HDL-C ratio increased by 0.18 (95% CI: 0.11, 0.25), with no change in non-HDL-C or triglycerides. Changes in HDL-C and the TC/HDL-C ratio associated with pregnancy persisted for decades, leading to altered life-course lipid trajectories. For example, parous women had a lower HDL-C than nulliparous women at the age of 50 years (-1.4 mg/dl; 95% CI: -2.3, -0.4). Adverse changes in lipids were greatest after first birth, with small changes after subsequent births, and were larger in women who did not breastfeed. Findings suggest that pregnancy is associated with long-lasting adverse changes in HDL-C, potentially setting parous women on a more atherogenic trajectory than prior to pregnancy.  
  Address Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA  
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  Series Volume Series Issue Edition  
  ISSN 0022-2275 ISBN Medium  
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  Notes PMID:30314998; PMCID:PMC6277164 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 2132  
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Author Petursson, H.; Sigurdsson, J.A.; Bengtsson, C.; Nilsen, T.I.L.; Getz, L. url  doi
  Title Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study Type Journal Article
  Year 2012 Publication Journal of Evaluation in Clinical Practice Abbreviated Journal J Eval Clin Pract  
  Volume 18 Issue 1 Pages 159-168  
  Keywords Adult; Aged; *Algorithms; Cardiovascular Diseases/mortality; Cholesterol/*blood; Humans; Middle Aged; Norway; *Practice Guidelines as Topic; Proportional Hazards Models; Prospective Studies; Risk Factors; Young Adult  
  Abstract RATIONALE, AIMS AND OBJECTIVES: Many clinical guidelines for cardiovascular disease (CVD) prevention contain risk estimation charts/calculators. These have shown a tendency to overestimate risk, which indicates that there might be theoretical flaws in the algorithms. Total cholesterol is a frequently used variable in the risk estimates. Some studies indicate that the predictive properties of cholesterol might not be as straightforward as widely assumed. Our aim was to document the strength and validity of total cholesterol as a risk factor for mortality in a well-defined, general Norwegian population without known CVD at baseline. METHODS: We assessed the association of total serum cholesterol with total mortality, as well as mortality from CVD and ischaemic heart disease (IHD), using Cox proportional hazard models. The study population comprises 52 087 Norwegians, aged 20-74, who participated in the Nord-Trondelag Health Study (HUNT 2, 1995-1997) and were followed-up on cause-specific mortality for 10 years (510 297 person-years in total). RESULTS: Among women, cholesterol had an inverse association with all-cause mortality [hazard ratio (HR): 0.94; 95% confidence interval (CI): 0.89-0.99 per 1.0 mmol L(-1) increase] as well as CVD mortality (HR: 0.97; 95% CI: 0.88-1.07). The association with IHD mortality (HR: 1.07; 95% CI: 0.92-1.24) was not linear but seemed to follow a 'U-shaped' curve, with the highest mortality <5.0 and >/=7.0 mmol L(-1) . Among men, the association of cholesterol with mortality from CVD (HR: 1.06; 95% CI: 0.98-1.15) and in total (HR: 0.98; 95% CI: 0.93-1.03) followed a 'U-shaped' pattern. CONCLUSION: Our study provides an updated epidemiological indication of possible errors in the CVD risk algorithms of many clinical guidelines. If our findings are generalizable, clinical and public health recommendations regarding the 'dangers' of cholesterol should be revised. This is especially true for women, for whom moderately elevated cholesterol (by current standards) may prove to be not only harmless but even beneficial.  
  Address Research Unit of General Practice, Department of Public Health and General Practice, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. halfdanpe@gmail.com  
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  Series Volume Series Issue Edition  
  ISSN 1356-1294 ISBN Medium  
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  Notes PMID:21951982; PMC3303886 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1567  
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Author Rangul, V.; Bauman, A.; Holmen, T.L.; Midthjell, K. url  doi
  Title Is physical activity maintenance from adolescence to young adulthood associated with reduced CVD risk factors, improved mental health and satisfaction with life: the HUNT Study, Norway Type Journal Article
  Year 2012 Publication The International Journal of Behavioral Nutrition and Physical Activity Abbreviated Journal Int J Behav Nutr Phys Act  
  Volume 9 Issue Pages 144  
  Keywords Adolescent; Adult; Blood Pressure; Body Composition; Body Mass Index; Cardiovascular Diseases/*prevention & control; Cholesterol, HDL/blood; Cross-Sectional Studies; Female; Follow-Up Studies; Health Status; Health Surveys; Humans; *Life Style; Linear Models; Logistic Models; Longitudinal Studies; Male; *Mental Health; *Motor Activity; Norway; Prospective Studies; Risk Factors; Self Report; Triglycerides/blood; Waist Circumference; Young Adult  
  Abstract BACKGROUND: Little is known about the effect maintaining physical activity throughout adolescence has on cardiovascular risk factors and health status in early adulthood. This ten-year prospective longitudinal study investigated whether differences in physical activity patterns from adolescence to young-adulthood showed different associations with subsequent cardio-metabolic risk factors and mental health in young-adulthood. METHODS: Based on the second and third Norwegian Nord-Trondelag Health Surveys (HUNT2 and 3), we included 1869 individuals (838 males) participating in Young-HUNT (1995-97), aged 13-19 years and followed-up at HUNT3 (2006-08), aged 23-31. Self-reported physical activity (PA), mental health and perceived health were recorded, along with measurements of body mass index (BMI), waist circumference (WC), total cholesterol (TC), HDL cholesterol, glucose, triglycerides, resting heart rate (HR) and blood pressure. We used separate linear regressions models to investigate associations between physical activity and each CVD risk factor, and logistic regression analysis to examine PA patterns and subsequent mental health. Physically active maintainers were compared to inactive maintainers. Adopters (inactive as adolescents and physically active as young adults) were compared to inactive maintainers and to those who discontinued activity (relapsers). RESULTS: Active maintainers had significantly lower HR, compared to all other PA patterns. Active maintaining men had significantly lower WC than relapsers and inactive maintainers. When adjusted for age and gender, WC, BMI, HR, diastolic blood pressure and HDL-C showed significant differences comparing active maintaining to other PA patterns. Comparing inactive maintainers against adopters, only HR was significantly lower. Male adopters did not differ significantly in CVD risk compared to inactive maintainers and relapsers. Among females adopting was associated with lower HR and TC compared to inactive maintainers. Active maintainers showed better mental health than inactive maintainers. Active maintaining males had an increased likelihood of good mental health compared to adopters. Active maintaining females reported greater satisfaction with life compared to adopters. CONCLUSIONS: Those who maintained their physical activity from adolescence to young adulthood demonstrated a significantly lower CVD risk and better mental health, compared to inactive maintainers. Compared to inactivity maintainers and relapsers, adopting physical activity was not significantly associated with lowered CVD risk. Adopting physical activity between adolescence and young adulthood may not necessarily protect against mental distress.  
  Address Nord-Trondelag University College, Levanger, Norway. vegar.rangul@hint.no  
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  ISSN 1479-5868 ISBN Medium  
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  Notes PMID:23241306; PMC3541207 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1568  
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Author Tang, C.S.; Zhang, H.; Cheung, C.Y.; Xu, M.; Ho, J.C.; Zhou, W.; Cherny, S.S.; Zhang, Y.; Holmen, O.; Au, K.W.; Yu, H.; Xu, L.; Jia, J.; Porsch, R.M.; Sun, L.; Xu, W.; Zheng, H.; Wong, L.Y.; Mu, Y.; Dou, J.; Fong, C.H.; Wang, S.; Hong, X.; Dong, L.; Liao, Y.; Wang, J.; Lam, L.S.; Su, X.; Yan, H.; Yang, M.L.; Chen, J.; Siu, C.W.; Xie, G.; Woo, Y.C.; Wu, Y.; Tan, K.C.; Hveem, K.; Cheung, B.M.; Zollner, S.; Xu, A.; Eugene Chen, Y.; Jiang, C.Q.; Lam, T.H.; Ganesh, S.K.; Huo, Y.; Sham, P.C.; Lam, K.S.; Willer, C.J.; Tse, H.F.; Gao, W.   
  Title Exome-wide association analysis reveals novel coding sequence variants associated with lipid traits in Chinese Type Journal Article
  Year 2015 Publication Nat Commun Abbreviated Journal Nature communications  
  Volume 6 Issue Pages 10206  
  Keywords Asian Continental Ancestry Group/*genetics; Cholesterol, HDL/metabolism; Cholesterol, LDL/metabolism; Exome/*genetics; *Genetic Variation; Genotype; Humans; Lipid Metabolism/*genetics; Triglycerides/metabolism  
  Abstract Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Department of Psychiatry, the University of Hong Kong, Hong Kong, China.Department of Internal Medic Editor  
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  Call Number HUNT @ maria.stuifbergen @ Tang2015 Serial 1866  
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Author Wu, Y.; Waite, L.L.; Jackson, A.U.; Sheu, W.H.-H.; Buyske, S.; Absher, D.; Arnett, D.K.; Boerwinkle, E.; Bonnycastle, L.L.; Carty, C.L.; Cheng, I.; Cochran, B.; Croteau-Chonka, D.C.; Dumitrescu, L.; Eaton, C.B.; Franceschini, N.; Guo, X.; Henderson, B.E.; Hindorff, L.A.; Kim, E.; Kinnunen, L.; Komulainen, P.; Lee, W.-J.; Le Marchand, L.; Lin, Y.; Lindstrom, J.; Lingaas-Holmen, O.; Mitchell, S.L.; Narisu, N.; Robinson, J.G.; Schumacher, F.; Stancakova, A.; Sundvall, J.; Sung, Y.-J.; Swift, A.J.; Wang, W.-C.; Wilkens, L.; Wilsgaard, T.; Young, A.M.; Adair, L.S.; Ballantyne, C.M.; Buzkova, P.; Chakravarti, A.; Collins, F.S.; Duggan, D.; Feranil, A.B.; Ho, L.-T.; Hung, Y.-J.; Hunt, S.C.; Hveem, K.; Juang, J.-M.J.; Kesaniemi, A.Y.; Kuusisto, J.; Laakso, M.; Lakka, T.A.; Lee, I.-T.; Leppert, M.F.; Matise, T.C.; Moilanen, L.; Njolstad, I.; Peters, U.; Quertermous, T.; Rauramaa, R.; Rotter, J.I.; Saramies, J.; Tuomilehto, J.; Uusitupa, M.; Wang, T.-D.; Boehnke, M.; Haiman, C.A.; Chen, Y.-D.I.; Kooperberg, C.; Assimes, T.L.; Crawford, D.C.; Hsiung, C.A.; North, K.E.; Mohlke, K.L. url  doi
  Title Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained Type Journal Article
  Year 2013 Publication PLoS Genetics Abbreviated Journal PLoS Genet  
  Volume 9 Issue 3 Pages e1003379  
  Keywords African Americans/genetics; Apolipoproteins A/*genetics; Cholesterol, HDL/blood/genetics; Cholesterol, LDL/blood/genetics; European Continental Ancestry Group/genetics; *Genome-Wide Association Study; Humans; Lipoproteins, HDL/blood/genetics; Lipoproteins, LDL/blood/genetics; Proprotein Convertases/*genetics; Serine Endopeptidases/*genetics; Triglycerides/blood/genetics  
  Abstract Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1 x 10(-4) in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies.  
  Address Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, United States of America  
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  Language English Summary Language Original Title  
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  ISSN 1553-7390 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23555291; PMC3605054 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1385  
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